PMID- 36532784
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221221
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Post-marketing safety of immunomodulatory drugs in multiple myeloma: A 
      pharmacovigilance investigation based on the FDA adverse event reporting system.
PG  - 989032
LID - 10.3389/fphar.2022.989032 [doi]
LID - 989032
AB  - Objective: In recent years, the emergence of immunomodulatory drugs (IMiDs) has 
      significantly improved clinical outcomes in patients with multiple myeloma (MM); 
      however, serious adverse events (AEs) have hindered their safe clinical 
      application. This study aimed to characterize the safety profiles and differences 
      in IMiDs through a disproportionality analysis using the U.S. Food and Drug 
      Administration Adverse Event Reporting System (FAERS), a post-marketing 
      surveillance database. Methods: This study filtered reports of thalidomide, 
      lenalidomide, and pomalidomide as primary suspect drugs in FAERS files from 
      January 2013 to December 2021. AEs in the reports were retrieved according to the 
      preferred terms (PTs) of the Medical Dictionary for Regulatory Activities. 
      Furthermore, we detected safety signals using the reporting odds ratio (ROR), 
      proportional reporting ratio (PRR), and Bayesian belief propagation neural 
      network (BCPNN). When all three algorithms showed an association between the 
      target drug and the AE, a positive signal was generated. Results: We extracted 
      9,968 thalidomide, 231,926 lenalidomide, and 55,066 pomalidomide AE reports. AEs 
      were more common in male patients and in those >44 years old. Important safety 
      signals were detected based on the system organ classes (SOC), including 
      thalidomide (cardiac disorders: ROR, 2.87; PRR, 2.79; IC 1.22), lenalidomide 
      (gastrointestinal disorders: ROR, 2.38; PRR, 2.27; IC 0.75), and pomalidomide 
      (respiratory, thoracic, and mediastinal disorders: ROR, 2.14; PRR, 2.09; IC 
      0.85). Within the PT level, we identified novel risk signals: the 
      thalidomide-induced second primary malignancy (SPM) signal was significant; 
      lenalidomide reduced the success rate of hematopoietic stem cell collection; and 
      three IMiDs may cause human chorionic gonadotropin increase, but this needs to be 
      proven by clinical data. Pneumonia, sepsis, and renal failure are common risk 
      factors for death due to IMiDs. Compared with thalidomide and lenalidomide, 
      pomalidomide has a lower risk of venous thromboembolism (VTE) and is beneficial 
      to patients with renal insufficiency. Conclusion: Mining data from FAERS resulted 
      in novel AE signals, including adenocarcinoma of colon, harvest failure of blood 
      stem cells, and increased levels of human chorionic gonadotropin. Further 
      investigation is required to verify the significance of these signals. Moreover, 
      IMiDs showed differences in safety reports, which should be emphasized by 
      clinicians.
CI  - Copyright (c) 2022 Jiang, Su, Li, Wu, Ming, Li, Fu, Feng, Li, Li, Ni and Liu.
FAU - Jiang, Tingting
AU  - Jiang T
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Su, Hui
AU  - Su H
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Li, Yanping
AU  - Li Y
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Wu, Yuanlin
AU  - Wu Y
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Ming, Yue
AU  - Ming Y
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Li, Chen
AU  - Li C
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Fu, Ruoqiu
AU  - Fu R
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Feng, Lu
AU  - Feng L
AD  - State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and 
      Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, 
      China.
FAU - Li, Ziwei
AU  - Li Z
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Li, Li
AU  - Li L
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Ni, Rui
AU  - Ni R
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
FAU - Liu, Yao
AU  - Liu Y
AD  - Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20221201
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9751748
OTO - NOTNLM
OT  - FAERS
OT  - IMiDs
OT  - adverse event
OT  - data mining
OT  - multiple myeloma
OT  - pharmacovigilance
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/12/20 06:00
MHDA- 2022/12/20 06:01
PMCR- 2022/12/01
CRDT- 2022/12/19 04:21
PHST- 2022/07/08 00:00 [received]
PHST- 2022/11/18 00:00 [accepted]
PHST- 2022/12/19 04:21 [entrez]
PHST- 2022/12/20 06:00 [pubmed]
PHST- 2022/12/20 06:01 [medline]
PHST- 2022/12/01 00:00 [pmc-release]
AID - 989032 [pii]
AID - 10.3389/fphar.2022.989032 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Dec 1;13:989032. doi: 10.3389/fphar.2022.989032. 
      eCollection 2022.